Application of chemokine receptor antagonist with stents reduces local inflammation and suppresses cancer growth
- 203 Downloads
Severe pain and obstructive jaundice resulting from invasive cholangiocarcinoma or pancreatic carcinoma can be alleviated by implantation of biliary and duodenal stents. However, stents may cause local inflammation to have an adverse effect on the patients’ condition and survival. So far, no efficient approaches have been applied to prevent the occurrence of stents-related inflammation. Here, we reported significantly higher levels of serum stromal cell-derived factor 1 (SDF-1) in the patients that developed stents-associated inflammation. A higher number of inflammatory cells have been detected in the cancer close to stent in the patients with high serum SDF-1. Since chemokine plays a pivotal role in the development of inflammation, we implanted an Alzet osmotic pump with the stents to gradually release AMD3100, a specific inhibitor binding of SDF-1 and its receptor C-X-C chemokine receptor 4 (CXCR4), at the site of stents in mice that had developed pancreatic cancer. We found that AMD3100 significantly reduced local inflammation and significantly inhibited cancer cell growth, resulting in improved survival of the mice that bore cancer. Moreover, the suppression of cancer growth may be conducted through modulation of CyclinD1, p21, and p27 in the cancer cells. Together, these data suggest that inhibition of chemokine signaling at the site of stents may substantially improve survival through suppression of stent-related inflammation and tumor growth.
KeywordsPancreatic cancer Stents Inflammation Stromal cell-derived factor 1 (SDF-1)
Conflicts of interest
- 7.Katsinelos P, Kountouras J, Germanidis G, Paroutoglou G, Paikos D, Lazaraki G, et al. Sequential or simultaneous placement of self-expandable metallic stents for palliation of malignant biliary and duodenal obstruction due to unresectable pancreatic head carcinoma. Surg Laparosc Endosc Percutan Tech. 2010;20:410–5.CrossRefPubMedGoogle Scholar
- 27.Xu H, Sun Y, Zhang Y, Wang W, Dan J, Yao J, et al. Protoporphyrin IX induces a necrotic cell death in human THP-1 macrophages through activation of reactive oxygen species/c-Jun N-terminal protein kinase pathway and opening of mitochondrial permeability transition pore. Cell Physiol Biochem. 2014;34:1835–48.CrossRefPubMedGoogle Scholar